bioRxiv Preprints

{
  "doi": "10.64898/2026.07.27.740917",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740917v1",
  "title": "An integrated biomaterials-centred approach of the ageing thymic microenvironment reveals design principles for regenerative biomaterials",
  "source": "biorxiv",
  "authors": "Di Bernarndo, A.; Zanirato, C.; Briatico, F.; Petrini, P.; Butnarasu, C. S.; Leo, F.; Ambrogio, C.; Patrucco, E.; Locatelli, A.; Oliva, F.; Passoni, A.; Medana, C.; Visentin, S.; Sardelli, L.",
  "version": "1",
  "abstract": "Thymic involution is commonly addressed as a loss of epithelial and lymphoid tissue, yet the accompanying remodelling of the microenvironment remains poorly defined. This work applied a biomaterials-centered approach to compare young and aged bovine thymus by integrating histology, oscillatory rheology, untargeted lipidomics, ICP-MS and AP-MALDI mass spectrometry imaging. This holistic approach connects the mechanical, compositional, and spatial features of the native thymus with the development of thymus-inspired biomaterials. Ageing increased both storage and loss moduli by more than one order of magnitude and reduced the linear viscoelastic region approximately fivefold, defining a markedly stiffer and more strain-sensitive material state. This mechanical transition was accompanied by lipid remodelling, with double realtive contribution of triacylglycerols to the lipid pool doubled and loss of membrane-associated phospholipids. The elemental profile also contracted, with total metal content decreasing by one-third and zinc showing a reduction of 70%. At the architectural level, the corticomedullary ratio was more than halved, while AP-MALDI imaging revealed an approximately 40% ",
  "category": "bioengineering",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Lorenzo Sardelli",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Molecular Biotechnology and Health Science, University of Torino, Torino, Italy"
}

{
  "doi": "10.64898/2026.07.26.740815",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.26.740815v1",
  "title": "Coupling Luciferase Activation and BRET Enables High-Contrast Red-Window Calcium Imaging",
  "source": "biorxiv",
  "authors": "Sharma, R.; Xiong, Y.; Tian, X.; Ai, H.",
  "version": "1",
  "abstract": "Genetically encoded bioluminescent calcium indicators enable excitation-free imaging of Ca2+ dynamics with low background, no photobleaching, and improved tissue penetration. However, many exhibit lower dynamic ranges than their fluorescent counterparts, motivating the development of new sensor configurations, particularly for imaging in the red optical window, where tissue absorption and scattering are reduced. Here, we developed HyBRIC and HyBRIC2, two hybrid indicators that integrate Ca2+-dependent luciferase activation and bioluminescence resonance energy transfer (BRET) within a single molecular architecture. When paired with pyCTZ luciferin, they exhibited an approximately 55-fold Ca2+-dependent signal increase in the red optical window in vitro. Compared with HyBRIC, HyBRIC2 showed improved brightness and responsiveness in mammalian cells. It robustly resolved induced Ca2+ dynamics in HEK293T and HeLa cells, with particularly strong red-window responses. Together, these findings expand the limited repertoire of responsive red-window bioluminescent calcium indicators and establish hybrid multiplicative sensing as a modular strategy for improving biosensor contrast.",
  "category": "biochemistry",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Huiwang Ai",
  "journal_published_doi": null,
  "corresponding_institution": "University of Virginia"
}

{
  "doi": "10.64898/2026.07.26.738612",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.26.738612v1",
  "title": "Computational evolutionary approach to generate antimicrobial peptides",
  "source": "biorxiv",
  "authors": "Harrison, T.; Zhang, T.; Parmar, M.; Praveen, P.; Menekse, A.; Darmawan, K. K.; Hung, A.; Li, W.",
  "version": "1",
  "abstract": "As a consequence of the overuse of conventional antibiotics, there is currently an unprecedented increase in antibiotic resistance in newer generations of pathogenic bacteria. This growing problem has led scientists to discover novel medications that could potentially reduce the usage of antibiotics, such as antimicrobial peptides (AMPs). Recent study has demonstrated that pardaxin could bind deeply into the surface of a lipid model membrane and inhibit the growth of pathogenic bacteria, including Staphylococcus aureus and Escherichia coli. In this work, the antibacterial efficacy of pardaxin was extended further by performing selective in silico substitution, driven by deep learning, Evolutionary-Scale Cambrian (ESMC) combined with conventional AMP design principles. Principal component analyses of the ESMC embeddings combined with conventional design models produced a set of single-and multiple-mutant analogues of pardaxin, which were predicted and validated with experimental data to exhibit selective antimicrobial properties against either E. coli or S. aureus, respectively. Atomistic molecular dynamics simulations further supported the notion that alpha-helical stability is a c",
  "category": "biochemistry",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Wenyi Li",
  "journal_published_doi": null,
  "corresponding_institution": "La Trobe University"
}

{
  "doi": "10.64898/2026.07.27.741005",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.741005v1",
  "title": "When Does Reaction Norm GWAS Discover Plasticity? The Residual Channel in Environmental Index-Based Genetic Dissection",
  "source": "biorxiv",
  "authors": "Jenkins, S. D.; Graef, G. L.",
  "version": "1",
  "abstract": "CERIS-JGRA replaces the environmental mean in Finlay-Wilkinson regression with a climate-derived index, so that reaction norm association mapping can dissect the genetics of phenotypic plasticity. Its defining design choice forecloses that objective. An index correlated at{rho} with the environmental means decomposes exactly into{rho} times the mean plus a residual, and its loading on informative variation orthogonal to the mean,{tau} , cannot exceed {surd}(1 -{rho} {superscript 2}). Sensitivity independent of mean performance is orthogonal to the mean by definition, reaching the slope only through{tau} , and the non-centrality of a plasticity-specific test goes as{tau} {superscript 2}. The algorithm maximizes{rho} , minimizing by construction the channel carrying the signal it is used to detect. Simulation confirms this. A parameter-free expression reproduces observed power across 189 conditions to a root mean square error of 0.030. Power to detect plasticity-specific loci falls from 0.64 at{rho} = 0 to 0.009 at{rho} = 0.99 and 0.003 at{rho} = 0.996, invariant to architecture, coupling and environment count. Holding{rho} at 0.5 while reducing{tau} from 0.87 to zero drops power fro",
  "category": "genetics",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Shawn D. Jenkins",
  "journal_published_doi": null,
  "corresponding_institution": "University of Nebraska-Lincoln"
}

{
  "doi": "10.1101/2025.11.02.686131",
  "url": "https://www.biorxiv.org/content/10.1101/2025.11.02.686131v3",
  "title": "Field persistence of entomopathogenic fungi and network-level associations within the soil microbial community as biocontrol agents",
  "source": "biorxiv",
  "authors": "Matveev, S.; Reingold, V.; Doron-Faigenboim, A.; Livne, Y.; Davidovitz, M.; Ment, D.",
  "version": "3",
  "abstract": "The effects of entomopathogenic fungi (EPF) on native soil microbiota are poorly understood. Here, we investigated the persistence of the EPF Metarhizium brunneum and Beauveria bassiana as preventive treatments for date palms against the red palm weevil, Rhynchophorus ferrugineus, and monitored the microbial community within the palms. We assessed the changes in the soil microbiota of the palms following application by fungal soil isolation techniques, high-throughput metagenomics, EPF persistence assays, and accompanied that with a continuous monitoring of date palm health. EPF preemptive treatments significantly improved palm protection against the weevil. While both EPF species persisted for 180 days post-application, their effectiveness diverged, with B. bassiana providing longer palm protection. Overall microbial community composition showed no major changes following EPF applications; however, transient alterations increased the relative abundance of local EPF genera, with dominant taxa being more likely to persist. Both EPF treatments enhanced the relative abundance of nitrogen-fixing bacteria, organic matter decomposers, and ammonia-oxidizing archaea, suggesting potential i",
  "category": "ecology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Dana Ment",
  "journal_published_doi": null,
  "corresponding_institution": "ARO"
}

{
  "doi": "10.64898/2026.07.22.740081",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.22.740081v1",
  "title": "The consequences of mixed-mode transmission for disease prevalence",
  "source": "biorxiv",
  "authors": "Amundson, I.; Antonovics, J.",
  "version": "1",
  "abstract": "Host-parasite relationships are defined by transmission. Transmission takes diverse forms, with horizontal transmission modes generally characterized as density- or frequency-dependent. However, many observed parasites display mixed-mode transmission using both density- and frequency-dependent routes. To investigate how mixed-mode transmission impacts epidemics, we assessed infection prevalence under single- and mixed-mode transmission when there was a linear trade-off between the probability of infection by the two modes. Our results show that the prevalence of a parasite with mixed-mode transmission can be greater than one with a single-mode only when density- and frequency-dependent routes are associated with different effects of the parasite on host fitness. This work shows that mixed transmission modes per se may not necessarily increase disease prevalence, and that substituting two transmission modes for a single one may result in higher prevalence under limited conditions.",
  "category": "ecology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Irish Amundson",
  "journal_published_doi": null,
  "corresponding_institution": "University of Virginia"
}

{
  "doi": "10.64898/2026.07.27.740871",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740871v1",
  "title": "Macronutrient balance generates distinct nutritional optima for growth, immune function and stress responses in the specialist herbivore Plutella xylostella",
  "source": "biorxiv",
  "authors": "Venkatesan, R.; Ghosh, A.",
  "version": "1",
  "abstract": "Nutrition plays a fundamental role in insect physiology, yet whether growth, immunity and stress responses share a common nutritional optimum remains poorly understood. Using the Geometric Framework for Nutrition, we investigated how dietary protein and carbohydrate balance regulate multiple physiological functions in the specialist herbivore Plutella xylostella. Growth was jointly determined by protein and carbohydrate intake, with maximal biomass accumulation constrained primarily by protein availability. Immune traits showed distinct nutritional optima: total hemocyte counts and phenoloxidase activity were maximised at intermediate protein-carbohydrate (P:C) ratios, whereas survival following Bacillus thuringiensis challenge depended predominantly on protein intake. Antioxidant and detoxification responses likewise varied non-linearly across the nutrient landscape, with individual enzyme systems each exhibiting distinct nutrient-dependent optima. Importantly, no single macronutrient balance simultaneously maximised growth, immune performance and oxidative homeostasis, demonstrating that these functions have divergent nutritional requirements. Together, these findings show that m",
  "category": "ecology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Radhika Venkatesan",
  "journal_published_doi": null,
  "corresponding_institution": "Indian Institute of Science Education and Research (IISER) Kolkata"
}

{
  "doi": "10.64898/2026.07.27.740960",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740960v1",
  "title": "Host genetics and social relationships jointly shape fitness-associated microbiome variation in a population of feral horses",
  "source": "biorxiv",
  "authors": "Stothart, M.; McLoughlin, P. D.; Wilson, A.; Poissant, J.",
  "version": "1",
  "abstract": "Gut microbiome variation is consequential for host fitness, but its contribution to adaptive evolution in host populations remains unclear. Although gut microbiome heritability has been demonstrated in humans, domesticated animals, and wildlife, no study has simultaneously assessed heritability of, and natural selection on, microbiome traits. Moreover, prior studies have not investigated whether non-genetic inheritance mechanisms (e.g., maternal and social transmission) could also contribute to microbiome-mediated adaptation. Using quantitative genetic animal models and shotgun metagenomic data from the long-term, individual-based study of feral Sable Island horses (2394 samples, 794 known-fate individuals), we estimated additive genetic, maternal, and social contributions to fitness-associated dimensions of the microbiome identified using canonical analyses of principal coordinates. Combined, additive genetic, permanent environment, and social effects explained 47% and 38% of the variance in fitness-associated dimensions of microbiota or microbial gene family profiles, respectively, with social effects being 2-4 times stronger than additive genetic effects on average. Contrary to ",
  "category": "ecology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Mason Stothart",
  "journal_published_doi": null,
  "corresponding_institution": "University of Calgary"
}

{
  "doi": "10.64898/2026.01.29.702647",
  "url": "https://www.biorxiv.org/content/10.64898/2026.01.29.702647v2",
  "title": "H4K20me3 and CTCF act reciprocally at TAD boundaries to regulate cell state transitions",
  "source": "biorxiv",
  "authors": "Atai, K.; Mitra, M.; Bohn, E.; Hu, R.; Corvalan, A.; Jelinek, D.; Voisin, L.; Ambrus, A.; Sarathy, K.; Sparks, W. M.; Bonitto, K.; Dunkwu, A.; Coller, H. A.",
  "version": "2",
  "abstract": "Reversible transitions between proliferative and quiescent cell states involve widespread gene expression changes despite stable topologically associating domain (TAD) positioning. We report a reciprocal antagonism between TAD boundary element CTCF and histone modification H4K20me3 as a central mechanism governing the proliferation-quiescence transition. Genome-wide studies and functional perturbations reveal that elevated H4K20me3 in quiescent fibroblasts displaces CTCF at specific TAD boundaries while CTCF binding predominates in proliferating cells. H4K20me3 reversibly induces a compact chromatin state, elliptical nuclear morphology, and transcriptional programs associated with quiescence. Conversely, CTCF binding drives open chromatin, proliferative gene expression, and cell division despite quiescence signals. Fibroblasts lacking H4K20me3 methyltransferase KMT5C/Suv4-20h2 are hyper-proliferative and KMT5C-deficient mice are larger. Our findings provide a mechanistic framework for how architectural and epigenetic regulators exchange at TAD boundaries to coordinate reversible cell state transitions, a finding with implications for development and diseases of dysregulated prolife",
  "category": "cell biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Hilary A. Coller",
  "journal_published_doi": null,
  "corresponding_institution": "Department of Molecular, Cell and Developmental biology, UCLA, Los Angeles, CA, 90095; Department of Biological Chemistry, David Geffen School of Medicine, UCLA"
}

{
  "doi": "10.64898/2026.07.27.740939",
  "url": "https://www.biorxiv.org/content/10.64898/2026.07.27.740939v1",
  "title": "Live single-molecule imaging reveals global shifts in mRNA mobility during human stem cell differentiation",
  "source": "biorxiv",
  "authors": "Bamford, A.-D.; Gut, G.; Bucholz, T.-O.; Okamoto, R.; Seimiya, M.; Santel, M.; Treutlein, B.; Voigt, F.",
  "version": "1",
  "abstract": "Spatiotemporal regulation of mRNA localisation is fundamental to cell identity specification and function, yet tracking transcript dynamics in living differentiating cells remains technically challenging. Here, we establish a robust pipeline for MS2 tagging of endogenous transcripts in human induced pluripotent stem cells (iPSCs), coupled with single-particle tracking and Hidden Markov Modelling to map mRNA mobility landscapes during differentiation and cell state transitions. Applying this approach to different cytoskeleton-encoding transcripts in diverse contexts -- neural organoids, directly programmed neurons, and vascular organoids -- we reveal a conserved principle: Both, {beta}-actin and {beta}2b-tubulin particle dynamics progressively shift towards constrained, compartmentalised patterns as cells acquire cell type identity. Perturbation experiments demonstrate that microtubule-dependent tethering is a common, conserved mechanism controlling {beta}-actin mRNA localisation in all cell types studied, whereas translation-dependent anchoring and actin filaments contribute in a context-dependent manner. Analysis of particle dynamics in migrating blood vessel progenitors further s",
  "category": "cell biology",
  "published_at": "2026-07-28T00:00:00.000Z",
  "corresponding_author": "Franka Voigt",
  "journal_published_doi": null,
  "corresponding_institution": "University of Zurich"
}